Clinical Implication of Mycophenolic Acid Trough Concentration Monitoring in Kidney Transplant Patients on a Tacrolimus Triple Maintenance Regimen: A Single-Center Experience

Abstract

BACKGROUND This study was designed to analyze the clinical implications of mycophenolic acid trough concentration monitoring. MATERIAL AND METHODS We collected data of patients with mycophenolic acid trough concentration monitoring after their first kidney transplant between November 2006 and March 2015 who were prescribed tacrolimus, mycophenolate, and methylprednisolone. Analyses were performed on 3 periods: 1 month, 1 month to 1 year, and after 1 year post-transplantation. To analyze factors related to acute cellular rejection, logistic regression was used for 1 month, while Cox analysis was used during 1 month to 1 year and after 1 year post-transplantation. RESULTS In the 145 patients receiving mycophenolate mofetil, mean tacrolimus trough ≥7.0 ng/mL (OR=0.177, CI=0.060-0.524, p=0.002) and mean mycophenolic acid trough ≥1.7 mg/L (OR=0.190, CI=0.040-0.896, p=0.036) were protective for rejection during 1 month. Mean mycophenolic acid trough ≥1.7 mg/L (HR=0.179, CI=0.040-0.806, p=0.025) and ≥0.7 mg/L (HR=0.142, CI=0.028-0.729, p=0.019) were related to better rejection-free survival during 1 month to 1 year and after 1 year, respectively. In 399 patients receiving enteric-coated mycophenolate sodium, mean tacrolimus trough ≥7.0 ng/mL (OR=0.258, CI=0.131-0.507, p<0.001) and mean mycophenolic acid trough ≥2.1 mg/L (OR=0.507, CI=0.264-0.973, p=0.041) were protective for rejection during 1 month. Mean mycophenolic acid trough ≥1.7 mg/L (HR=0.519, CI=0.289-0.932, p=0.028) and ≥0.7 mg/L (HR=0.208, CI=0.072-0.602, p=0.004) were related to better rejection-free survival during 1 month to 1 year and after 1 year, respectively. CONCLUSIONS Mycophenolic acid trough concentration monitoring can be useful in preventing acute cellular rejection in patients receiving tacrolimus, mycophenolate, and methylprednisolone.

Figure 1

The correlations between mean MMF or EC-MPS dosages and mean MPA trough levels analyzed by simple linear regression. (Aa) patients receiving MMF showed a significant relationship during the total time period (p=0.002). (Ab) While the correlation was not significant within 1 month (p=0.161), (Ac, Ad) 1 month to 1 year and >1 year post-KT showed significant correlations (p<0.001, both). (Ba) patients receiving EC-MPS also showed a significant relationship during the total period (p=0.002). (Bb) There was no correlation within 1 month (p=0.161), (Bc, Bd) but 1 month to 1 year and >1 year post-KT showed a significant correlation (p<0.001, both).

Figure 2

Univariable Cox analyses show that (A) patients receiving MMF with a mean MPA trough level under 1.7 mg/L demonstrate a significant risk of BPAR-free survival compared to patients with mean MPA trough level over 1.7 mg/L during 1 month to 1 year, and mean MPA trough level under 0.7 mg/L demonstrate a significant risk of BPAR-free survival compared to patients with mean MPA trough level over 0.7 mg/ (B) >1 year after kidney transplantation.

Figure 3

Multivariable Cox analyses show that patients receiving EC-MPS with a mean MPA trough level under 1.7 mg/L demonstrate a significant risk of BPAR-free survival compared to patients with mean MPA trough level over 1.7 mg/L during (A) 1 month to 1 year, and mean MPA trough level under 0.7 mg/L demonstrate a significant risk of BPAR-free survival compared to patients with mean MPA trough level over 0.7 mg/ (B) >1 year after kidney transplantation.